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Autoimmune Insulin-dependent diabetes mellitus (Type 1): (IDDM-type 1). -IDDM is a type of diabetes that results from autoimmune destruction of insulin-producing pancreatic beta cells of the islets of Langerhans . - Incidence varies from ( 8 to 17 ) per 100,000 in Northern

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autoimmune insulin dependent diabetes mellitus type 1 iddm type 1

Autoimmune Insulin-dependent diabetes mellitus (Type 1): (IDDM-type 1)

-IDDM is a type of diabetes that results from autoimmune

destruction of insulin-producing pancreatic beta cells of

the islets of Langerhans.

-Incidence varies from (8 to 17) per 100,000 in Northern

Europe and USA (Highest in Scandinavia: 35 per

100,000) to a very low of 1 per 100,000 in Japan and

China.

causes of beta cells destruction

Causes of beta-cells destruction:

IDDM type 1 is induced by one or more of the following:

1-Getetic susceptibility:

-Type 1 IDDM is a polygenic disease; more then one

gene could be involved in establishment of this type.

-The strongest gene IDDM1(on one locus or more;

dominant or recessive) that located in the MHC Class II

gene region on chromosome 6 at region 6p21.

- IDDM2 locus on chromosome 11 ( 11p15).

-The expression of HLA-DR 3,4 haplotype by beta cells.

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2-The Viral infection of beta cells:

-Some types of viruses could cause virus-triggered

autoimmune response against the infected beta cells;

due to antigenic cross-reactivity.

Example: Coxsackievirustypes B3 and B4, Rubellavirus.

3-Environmental factors:

-Allergies against chemicals or drugs that change the

antigenic nature of beta-cell surface proteins.

major immunologic features of iddm type 1

Major immunologic Features of IDDM type 1:

1- HLA-DR3 and DR4 haplotype expression on the beta

cells of the islets of Langerhans.

2-Presence of reactive Autoantibodies directed against

multiple antigens of islets beta cells.

3-Monocytic and lymphocyticinfiltration of islets of

Langerhans.

4-Some evidence for partial responses to

immunosuppressive therapy.

mechanism of autoimmune destruction of islet beta cells

Mechanism of Autoimmune destruction of islet beta cells:

-Some types of infectious agents:

coxsackievirustypes B3 and B4, Rubella virus, CMV,

Mumps virus, and some strains of influenza.

-Expression of MHC class II on the surface of beta cells.

-Presentation of Autoantigen ; Glutamic acid

decarboxylase, and tyrosine phosphatase (IA-2).

-APC (DC) , engulfment of Autoantigen, migration to

pancreatic lymph nodes, activation of helper cell.

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-Isotype switching of B lymphocytes.

- Circulating anti-GAD, Tyrosine phosphatase

autoantibodies.

-Specific T lymphocyte response; mainly CD8 cells

, and some CD4 and NK cells inside the pancreatic islets.

-Direct cytotoxicity to Beta cellsby:

1-ADDC Mechanism.

2-FasL-mediated killing of beta cells.

immunologic and diagnostic features of iddm type 1

Immunologic and diagnostic features of IDDM Type 1:

A-Immunofluorescent microscopy (monoclonal

antibodies staining) reveals:

1-Expression of HLA-DR3,4 on both beta cells and

infiltrating lymphocytes.

2-CD8-Cytotoxic suppressor phenotype.

3-Antibodies and complement present on beta cells.

B-Serology:

Detection of autoantibodies in patient serum is a

diagnostic feature for type 1 but NOT type 2.

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-The Auto-reactive antibodies are :

1-Anti-Glutamic acid decarboxylase antibodies.

2-Anti- tyrosine phosphatase antibodies.

-These autoantibodies could be localized in vitro.

C-Biochemistry:

-Fasting plasma Glucose: at or above 7.00mmol/L

(126 mg/dl).

-GTT: Plasma glucose at or above 11.1 mmol/L

(200 mg/dl).

-HbA1c: At or above 6.5%

adrenal insufficiency addison s disease

Adrenal Insufficiency: Addison’s Disease:

Adrenal insufficiency: the glands do not produce adequate amount of steroid hormones (primary Cortisol), but may include impaired production of aldosterone.

Cortisol is produced by adrenal cortex in response to stress and low level of glucocorticoids.

Cortisol is a strong Anti-inflammatory agent that inhibits

Cellular and humoral immunity.

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Cortisol down-regulates the production of large group of Interleukins (IL-2,IL-4,5,6); this results in suppression of TH subset-2 which has a major function in activation of B-lymphocytes.

So Cortisol is used mainly to treat diseases associated with antibodies –mediated immune response (Rheumatoid diseases, and allergies).

In Biochemistry:

Regulation of Glucose metabolism (gluconeogenesis).

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Types of Adrenal insufficiency:

1-Primary:

-70-80% of cases are due to autoimmune adrenal

disease (Addison’s disease).

-Other cases are due to congenital adrenal hyperplasia.

2-Secondary:

-Impairment of the pituitary gland or hypothalamus.

Causes of Adrenal insufficiency:

-Chronic: Mainly the Addison’s disease.

Others: Tuberculosis, hemochromatosis, and

Adrenoleukodystrophy.

adrenal insufficiency addison s disease1

Adrenal Insufficiency: Addison’s Disease:

Major Immunologic features:

-Circulating antibodies against adrenal cells are present.

-Complement is fixed on the surface of adrenal cells.

-It is associated with other autoimmune diseases.

-Strongassociation with HLA-DR3,4for 60% of cases.

Mechanism of adrenal cell destruction:

Expression of Auto-antigen 21-hydroxylase enzyme by

MHC class II on the surface of cell.

- Specific APC interaction.

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-Migration of APC to the lymph nodes.

-Activation of specific T helper cells.

-Monoclonal B lymphocyte isotype switching.

-Production of Auto-reactive antibodies.

-Attachment to cortical

cell surface.

-Complementfixation,

cellular destruction.

diagnostic features of addison s disease

Diagnostic features of Addison’s disease:

-Microscopy: lymphocytic infiltration.

-Immunofluorescence (direct) stainingshows:

1-Autoantibodies on the surface of cortical cells.

2-Complement fragments.

-Serum levels of adrenocorticotropic hormone (ACTH) are

elevated.

-Decreased serum Cortisol level.

-Increased serum potassium.

-Serology:

Detection of anti-21 hydroxylase antibodies in serum.

autoimmune polyglandular syndromes

Autoimmune polyglandular syndromes:

Major immunologic features:

-Circulating antibodies against multiple endocrine organs.

-HLA-DR expression on affected cells.

Type I syndrome:

-It occurs in childhood before 10 years.

-Oral Candidiasis and hypoparathyroidism (70% of cases).

-40-70 % of patients go on to develop adrenal

insufficiency.

-Minor association with Gonadal failure.

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Type II syndrome:

-It occurs mainly between the ages of 20-30 years.

-Has a 2:1 female predominance.

-familial inheritance of mutant allele.

-HLA-DR3 association.

-Major criteria: Adrenal failure, Thyroid disease,

and IDDM.

-Minor: Gonadal failure.

Type III syndrome:

-Autoimmune thyroid disease associated with IDDM or

Autoimmune Anti-intrinsic factor Abs (gastric disease).